Two of the goals of this project are the development of catalytic coupling reactions of alkynes and aldehydes (Section 1) and of alkynes and imines (Section 2). These methods effect a carbon-carbon bond formation and either a reduction or alkylation in the same operation, providing allylic alcohols and allylic amines, respectively. The products of these reactions are useful "chiral building blocks" in the preparation of more complex molecules with therapeutic benefits. In Section 3, asymmetric catalytic reductive coupling of alkynes and aldehydes is used as a means of macrocyclization or fragment coupling in the total synthesis of terpestacin and fusaproliferin. Terpestacin inhibits the progression of HIV infection, and it (or structurally related molecules) may provide a new means with which AIDS can be treated. Prof. David Chan (Caltech Biology) has developed the necessary assays for and has expressed a strong interest in studying terpestacin's mechanism of action. In preliminary studies related to Section l, highly enantioselective catalytic reductive couplings of alkynes and aldehydes (up to 95 percent ee) have been developed for certain types of alkynes and have led to the design of novel ligands that may be more selective and/or more general. For other types of alkynes another novel chiral phosphine ligand appears to be superior based on preliminary results. Initial studies related to Section 2 have shown that certain imines are effective coupling partners in both intramolecular and intermolecular three component coupling reactions, in which a group from an organoborane reagent is also incorporated in the tetrasubstituted allylic amine product. Preliminary studies related to Section 3 have focused on the preparation of advanced synthetic intermediates and have demonstrated the feasibility of the catalytic fragment coupling reactions.